Explore the complexities of Follicular Lymphoma, the most common indolent B-cell lymphoproliferative disorder
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Follicular Lymphoma (FL) is the most prevalent indolent B-cell lymphoproliferative disorder of malignant germinal follicular center B cells, characterized by a slow progression and a variable clinical course. Diagnosis typically involves histological examination through a biopsy of a lymph node or another affected tissue.
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Clinical manifestations of FL in Class 1-2 and 3A include inertia, while Class 3B presents with invasion similar to diffuse large B-cell lymphoma (DLBCL).
0 to 5 matricytes per high-power field
6 to 15 matricytes per high-power field
More than 15 matricytes per high-power field
Median age at diagnosis is 60 years
Median overall survival is more than 15 years
20% relapse within 2 years after 1L treatment
10% may transform over their lifetime
14,000 FL patients in the US annually
Indolent yet incurable disease
Some subsets exhibit significantly worse prognosis.
Roles of epigenetic modifiers and survival pathways are poorly understood
Unknown disease progression for patients
Most receive generic therapy irrespective of prognostic scores
~80% of FL mono-therapies are also approved for other B-cell lymphomas
Restricted precision medicine options in FL
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The progression and transformation of Follicular Lymphoma (FL) into more aggressive forms within a patient's lifetime are not fully understood. This heterogeneity adds to the complexity of treating and managing the disease effectively.
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FL remains a condition with high unmet medical needs, primarily due to the limited understanding of its mechanistic heterogeneity. Properly determining a patient’s prognosis is crucial for initial clinical management and influences subsequent treatment decisions.
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Current prognostic tools, which integrate clinical and biological characteristics, face significant limitations. These include a scarcity of patient data, a lack of cohort validation, challenges in multiparametric analysis, and an overall inability to predict specific patient outcomes reliably.
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Current prognostic tools, which integrate clinical and biological characteristics, face significant limitations. These include a scarcity of patient data, a lack of cohort validation, challenges in multiparametric analysis, and an overall inability to predict specific patient outcomes reliably.
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Advancing our understanding of FL involves focusing on smaller, yet critical, patient subgroups such as those with Progression Of Disease within 24 months (POD24) and transformed FL (tFL). Targeting these groups is essential for making meaningful progress toward the ultimate goal of curing the disease.
The selection of a specific treatment regimen depends on factors like the disease stage, patient co-morbidities, and the preferences of the physician and patient. Treatment selection lacks any markers identified as ancillary or surrogate for heightened risk of transformation. It's worth noting that a minority of patients may be "cured" after front-line therapy.
The challenge in effectively treating Follicular Lymphoma (FL) lies in Identifying and understanding the cellular and molecular determinants of tumor heterogeneity driving FL progression, treatment resistance, and transformation. Drivers of FL heterogenous evolution remain unclear and key biological questions need to be answered.
How can we identify the cancer progenitor cell (CPC) responsible for relapse and/or resistance to current treatments, and what is its co-dependence with the tumor microenvironment (TME)?
What clinical strategies can be developed to target the CPCs, potentially through designing new screens for ad hoc drugs and immunotherapies?
Can existing drugs be targeted early enough to effectively avoid or contain the relapse of Follicular Lymphoma?
Identifying and validating surrogate or ancillary biomarkers to predict disease progression and transformation is crucial. These biomarkers help inform treatment selection, enable response monitoring, and reduce the duration of ineffective therapies.
Developing innovations for FL in the private sector is challenging due to the disease's indolent nature and low incidence. The long outcome endpoints, modest incidence, and generally favorable survival rates do not drive strong interest or commitment among drug developers. Addressing the unbalanced risk/reward ratio is necessary to motivate further innovation.
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